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The Journal of Antimicrobial... May 2023Respiratory syncytial virus (RSV) is a leading cause of hospitalization and infant mortality worldwide. There are currently no approved vaccines against RSV, and... (Review)
Review
Respiratory syncytial virus (RSV) is a leading cause of hospitalization and infant mortality worldwide. There are currently no approved vaccines against RSV, and immunoprophylaxis with the mAb palivizumab is limited to extremely vulnerable infants in resource-rich settings due to its high cost and the need for monthly injections throughout the RSV season. Nirsevimab (formerly MEDI8897) is a highly potent, long-acting, human, recombinant mAb that received approval for the prevention of RSV infection in newborns and infants during their first RSV season from the EMA and the UK's Medicines and Healthcare products Regulatory Agency in November 2022 based on positive results in Phase 2b and 3 clinical trials. Nirsevimab targets the highly conserved site Ø of the prefusion conformation of the RSV fusion (F) protein and contains a triple amino acid substitution in the Fc domain that extends its half-life, allowing for a single dose to cover a typical RSV season in regions with temperate climates. In this article I review key attributes of nirsevimab with an emphasis on pharmacology, pharmacokinetics, antiviral activity, and the potential for resistance and escape variants. I also summarize current progress in clinical trials and consider future research priorities.
Topics: Humans; Infant, Newborn; Infant; Antiviral Agents; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus, Human
PubMed: 36922390
DOI: 10.1093/jac/dkad076 -
Infectious Diseases and Therapy Mar 2021Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children, and older or immunocompromised adults. Although... (Review)
Review
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children, and older or immunocompromised adults. Although aerosolized ribavirin was licensed for RSV treatment on the basis of data demonstrating a reduced need for supplemental oxygen, ribavirin use is limited because of issues with efficacy, safety, and cost. Currently, the treatment of RSV is primarily supportive. New antiviral treatments for RSV are in the early stages of development, but it will be years until any of these may be licensed by the US Food and Drug Administration (FDA). Palivizumab, an RSV monoclonal antibody [immunoprophylaxis (IP)], has demonstrated effectiveness in disease prevention and is the only licensed IP for RSV disease in specific high-risk pediatric populations. Although its efficacy is well established, some challenges that may interfere with its clinical use include cost, need for monthly injections, and changing policy for use by the American Academy of Pediatrics (AAP). Preventing RSV disease would be possible through RSV vaccine development (e.g., live-attenuated, vector-based subunit, or particle-based). Alternatively, new long-acting monoclonal antibodies have demonstrated promising results in early clinical trials. Despite scientific advances, until new agents become available, palivizumab should continue to be used to reduce RSV disease burden in high-risk patients for whom it is indicated.
PubMed: 33656652
DOI: 10.1007/s40121-020-00383-6 -
Cureus Mar 2023With an increasing global incidence in children younger than the age of five, respiratory syncytial virus (RSV) is one of the most common viral respiratory infections... (Review)
Review
With an increasing global incidence in children younger than the age of five, respiratory syncytial virus (RSV) is one of the most common viral respiratory infections worldwide. Despite the increasing number of cases among infants and young children, RSV can infect any age group; however, some individuals are more high risk than others. Premature infants, young children, elderly, and immunocompromised individuals are the most likely to suffer a more severe presentation of RSV in comparison to healthy adults. RSV is transmitted through respiratory droplets via direct contact with an infected individual or with contaminated surfaces. The viral genome of RSV consists of 11 proteins. Out of these 11, two proteins allow for the attachment of the virus to the respiratory epithelial cells and fusion with host cells. Upon fusion, the viral material transfers to the host cell, where viral replication occurs. It is important to acknowledge that an individual is considered infectious and can transmit the virus even before the symptomatic presentation of RSV begins. As long as the individual is shedding the virus, he or she is considered infectious. The length of viral shedding also differs depending on the severity of the infection, who is infected, and the underlying immune status of an individual. Currently, there is no definitive treatment for RSV; however, supportive therapy is considered the mainstay treatment. Some pharmaceutical treatments such as ribavirin have been FDA-approved; however, the administration is typically limited to children and infants. Palivizumab is also administered as an immune prophylaxis; however, both therapies are constantly at the end of a cost-effective debate due to their extensively expensive nature and questionable adverse effect profiles. Supportive therapy includes hydration, supplemental oxygen, and mechanical ventilation in hospitalized cases; however, most RSV cases can be treated as outpatient cases. Prevention techniques such as hand washing and maintaining social distancing are imperative to minimize the transmission of the virus as much as remotely possible.
PubMed: 37082497
DOI: 10.7759/cureus.36342 -
Journal of the Pediatric Infectious... Aug 2023In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar...
In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar safety profile to that of palivizumab and resulted in nirsevimab serum exposures associated with efficacy in healthy infants, supporting efficacy in this population at risk of severe RSV disease.
Topics: Infant; Child; Humans; Antibodies, Monoclonal; Antiviral Agents; Seasons; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Lung Diseases
PubMed: 37466917
DOI: 10.1093/jpids/piad052 -
Anales de Pediatria Oct 2023Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. (Review)
Review
INTRODUCTION
Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain.
OBJECTIVES
To provide recommendations for the administration of nirsevimab for prevention of RSV disease.
METHODS
The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions.
RESULTS
In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis.
CONCLUSIONS
Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.
Topics: Infant, Newborn; Infant; Humans; Child; Antiviral Agents; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Communicable Diseases; Respiratory Tract Infections; Bronchiolitis
PubMed: 37743207
DOI: 10.1016/j.anpede.2023.09.006 -
The Journal of Pediatrics Sep 2019
Topics: Academies and Institutes; Child; Gestational Age; Humans; Palivizumab; Pediatrics; United States
PubMed: 31204023
DOI: 10.1016/j.jpeds.2019.05.045 -
The New England Journal of Medicine Dec 2023
Topics: Humans; Palivizumab; Respiratory Syncytial Virus Infections; Antiviral Agents
PubMed: 38157505
DOI: 10.1056/NEJMe2312934 -
The Medical Letter on Drugs and... Oct 2023
PubMed: 37755690
DOI: 10.58347/tml.2023.1686a